The effects of a 20-week exercise program on blood-circulating biomarkers related to brain health in children with overweight or obesity: The ActiveBrains project.

BackgroundEmerging research supports that exercise positively affects neurodevelopment. However, the mechanisms linking exercise with brain health are largely unknown. We aimed to investigate the effect of exercise on (i) blood biomarkers selected based on previous evidence (brain-derived neurotrophic factor (BDNF), {beta}-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), vascular cell adhesion molecule-1 (sVCAM-1)); and (ii) a panel of 92 neurology-related proteins (discovery analysis). We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health (hippocampal structure and function, cognitive performance, and mental health). Methods81 children with overweight/obesity (10.1 {+/-}1.1 years, 41% girls) were randomized to either 20-week of aerobic plus resistance exercise or control. Candidate biomarkers were assessed using ELISA for Kynurenine, FGF21, and CTSB, colorimetry for BHB, and XMap for BDNF and VCAM-1. The 92 neurology-related proteins were analyzed by antibody-based proteomic analyses. ResultsOur intervention had no significant effect on candidate biomarkers (all p>0.05). In the discovery analysis, a reduction in circulating macrophage scavenger receptor type-I (MSR1) was observed (standardized differences between groups (SMD): -0.3, p=0.001). This effect was validated using ELISA methods (SMD: -0.3, p=0.01). None of the biomarkers mediated the effects of exercise on brain health. ConclusionsOur study does not support a chronic effect of exercise on candidate biomarkers. Nevertheless, we observed that chronic exercise reduced the levels of MRS1, while it did not mediate the effects of exercise on brain health. Future studies should explore the implications of this novel biomarker on general health. HighlightsO_LICandidate biomarkers (i.e., brain-derived neurotrophic factor (BDNF), {beta}-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), vascular cell adhesion molecule-1 (sVCAM-1)) did not mediate the effects of exercise on brain health outcomes. C_LIO_LIOur discovery analysis, a panel of 92 neurology-related proteins, identified a reduction effect of exercise on blood-circulating MRS1. C_LIO_LIExercise-induced changes in MRS1 did not mediate changes in brain health outcomes. C_LIO_LIThe MSR1 is a membrane glycoprotein, that has not been related to exercise before, expressed in macrophages, and involved in pathological processes such as atherosclerosis, non-alcoholic fatty liver disease, and neurological diseases. C_LIO_LIFuture studies should confirm the effect of exercise on MRS1 and its implications on general health. C_LI